Immunoregulation is important in the pathogenesis of leprosy. Leprosy is a disease of tissues not peripheral blood. Our investigations have shown the immune characteristics of lymphocytes in tissue lesions more closely reflect the host response than peripheral blood lymphocytes. The proposed study is designed to elucidate mechanisms of immunoregulation in leprosy by studying the nature of cells and their cytokines in tissue lesions by using monoclonal antibodies and immunoperoxidase techniques. Sequential biopsy tissue will be obtained to further study reactional states and immune changes induced by treatment modalities. We also plan to clone lymphocytes from tissue lesions and evaluate functional aspects of these cells such as suppressor cell activity. The information obtained should provide a new basis for therapeutic strategies. For example, it is proposed within that cyclosporin-A be given a trial as treatment for erythema nodosum leprosum based on immunopathologic data showing an in situ deinhibition of interleukin-2 production. This study should be undertaken because of the unique approach to immunoregulation in leprosy by evaluating tissue cells rather than peripheral blood cells.